Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform

Sheng Pan, John Rush, Elaine R. Peskind, Douglas Galasko, Kathryn Chung, Joseph Quinn, Joseph Jankovic, James B. Leverenz, Cyrus Zabetian, Catherine Pan, Yan Wang, Hun Oh Jung, Jean Gao, Jianpeng Zhang, Thomas Montine, Jing Zhang

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flighttandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.

Original languageEnglish (US)
Pages (from-to)720-730
Number of pages11
JournalJournal of Proteome Research
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Aging
  • Alzheimer's disease
  • Biomarker
  • Cerebrospinal fluid
  • Mass spectrometry
  • Matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)
  • Parkinson's disease
  • Quantitative proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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